Brain death: diagnosis

Instrumental methods to confirm the diagnosis of brain death

There are many problems in diagnosing the clinical criteria for brain death. Often, their interpretation is not enough to diagnose this condition with 100% accuracy. In this regard, already in the first descriptions, brain death was confirmed by stopping the bioelectric activity of the brain with the help of an EEG. Various methods to confirm the diagnosis of "brain death" have been recognized throughout the world. The need for their use is recognized by most researchers and clinicians. The only objections concern the diagnosis of "brain death" only by results of paraclinical studies without taking into account the data of the clinical examination. In most countries, they are used when it is difficult to conduct clinical diagnosis and when it is necessary to shorten the observation time in patients with a clinical picture of brain death.

Obviously, the methods by which to confirm the death of the brain must meet certain requirements: be carried out directly at the patient's bedside, do not take much time, be safe for both the subject and the potential recipient of the donor organs, as well as for the medical staff performing them, be as sensitive as possible, specific and protected from external factors. The proposed instrumental methods that allow diagnosing brain death can be divided into 3 types.

• Direct methods confirming the termination of biological activity of neurons: EEG, study of multimodal evoked potentials.
• Indirect methods, which confirm the cessation of intracranial blood flow and liquor pulsations: cerebral panangiography, TKDG, Echo, cerebral scintigraphy with sodium pertechnetate labeled ^99m Tc, subtraction intravene angiography, magnetic resonance angiography (MP angiography), spiral CT.
• Indirect methods that allow to detect a violation of the metabolism of the deceased brain: the determination of oxygen tension in the bulb of the jugular vein, infrared cerebral oximetry. They also include telethermography, since the temperature of various parts of the body reflects the level of metabolism of the organs and tissues to be treated. Attempts to use such modern methods for determining the level of cerebral energy metabolism, such as PET, diffusion and perfusion-weighted MRI programs, are also described.

Electroencephalography

EEG was the first method used to confirm the diagnosis of "brain death". The phenomenon of bioelectric silence of the brain was unequivocally regarded as a sign of the death of all brain neurons. A lot of research has been carried out to determine the sensitivity and specificity of the method. A general review conducted in 1990 showed that both sensitivity and specificity of the method are within 85%. Such relatively low indicators are due to low noise immunity of the EEG, which is especially evident in the intensive care unit where the patient is literally entangled with wires from the measuring equipment. The specificity of the EEG reduces the phenomenon of inhibition of brain bioelectrical activity in response to intoxication and hypothermia. Despite this, the EEG remains one of the main confirmatory tests, it is widely used in many countries. Since many different ways of fixing brain bioelectrical activity have been described, the staff of the American Electroencephalographic Society have developed recommendations that include minimum technical standards for EEG recording, necessary to confirm bioelectric silence of the brain. These parameters are legally prescribed in many countries and include the following formulations.

• The absence of electrical brain activity is established in accordance with the international provisions of EEG studies in conditions of brain death.
• For electric silence of the brain, an EEG record is taken in which the amplitude of activity from peak to peak does not exceed 2 μV, when recording from scalp electrodes with a distance between them not less than 10 cm and at a resistance of up to 10 kOhm, but not less than 100 Ω. Use needle electrodes, not less than 8, located in the "10-20" system, and two ear electrodes.
• It is necessary to determine the safety of commutations and the absence of unintentional or intentional electrode artifacts.
• Recording is carried out on the channels of the encephalograph with a time constant of at least 0.3 s with a sensitivity of no more than 2 μV / mm (upper limit of the frequency bandwidth is not lower than 30 Hz). Use devices that have at least 8 channels. EEG is recorded with bi-and unipolar leads. The electrical silence of the cerebral cortex under these conditions should be maintained for at least 30 minutes of continuous recording.
• If there are doubts in the electrical silence of the brain, it is necessary to re-register the EEG and evaluate the reactivity of the EEG to light, loud sound and pain: the total time of stimulation with light flashes, sound stimuli and pain stimuli is no less than 10 min. The source of flashes, fed at a frequency of 1 to 30 Hz, should be at a distance of 20 cm from the eyes. The intensity of the sound stimuli (clicks) is 100 dB. The speaker is located near the ear of the patient. Stimuli of maximum intensity are generated by standard photo- and photostimulators. For painful stimulations, strong needle pricks are used.
• EEG, recorded by phone, can not be used to determine the electrical silence of the brain.

Thus, the wide use of the EEG is facilitated by the high prevalence of both the instruments for recording it and by specialists who know the technique. It should also be noted the relative standardization of the EEG. But such shortcomings as low sensitivity to drug intoxication and poor immunity to interference, encourage additional use of more convenient and sensitive techniques.

Study of multimodal evoked potentials

Various components of the curve during registration of acoustic stem evoked potentials are generated by the corresponding sections of the auditory pathway. Wave I is generated peripheral auditory analyzer wave II - VIII in the proximal cranial nerve, in the transition region . N acusticus of the internal auditory meatus in the subarachnoid space, III-V components are generated by stem portions and cortical auditory pathway. The results of numerous studies indicate that to confirm the death of the brain, it is necessary to register the loss of waves from III to V. According to different authors, I-II components are also absent in primary registration in 26-50% of patients whose condition meets the criteria of brain death. However, in others, these components are detected despite the cessation of intracranial blood flow for several hours. Several explanations of this phenomenon are suggested, the most convincing of which is this assumption: since the pressure inside the labyrinth is somewhat lower than intracranial, residual perfusion remains after the onset of brain death in the labyrinthine artery basin. The same is confirmed by the fact that the venous outflow from the cochlea is protected from increased intracranial pressure by surrounding bone structures. Thus, to diagnose brain death, it is necessary to register the absence of III-V wave curves. At the same time, it is necessary to register I or 1 wave as a proof of the integrity of the peripheral part of the auditory analyzer, especially if the patient has a craniocerebral trauma.

The registration of SSEP allows to assess the functional state of both the trunk and the cerebral hemispheres. Currently, the SSEP is recorded in response to stimulation of the median nerve. The evoked responses can be registered over all areas of ascending afferentation. At death of the brain, the cortical components of the curve will not be recorded, while those recorded above the spinous process of the vertebra C _{II of the} wave N13a and P13 / 14 are seen in most cases. With the spread of the defeat caudal to the last recorded wave will be N13a above the vertebra C _VII. The ambiguous interpretation of the results of the SSVP record can cause extensive mechanical two-sided damage to the hemispheres or brainstem. In this case, the pattern of cortical response is identical to that of brain death. Of great interest is the work of Japanese authors who singled out the wave N18, recorded using a nasogastric electrode. According to their data, the disappearance of this component of the SSVP testifies to the death of the medulla oblongata. In the future, after carrying out the relevant large prospective studies, it is this version of the SSEP record that can replace the apneetic oxygenation test.

The visual pathway does not pass through the brainstem, therefore VZPs reflect only the pathology of the large hemispheres. At death of the brain, the VEP testifies to the absence of a cortical response with the possible preservation of the early negative component N50, which corresponds to the preserved electroretinogram. Therefore, the VIZ method does not have an independent diagnostic value and, according to the application spectrum, roughly corresponds to the usual EEG, the only difference being that it is more laborious and complex in interpretation.

Thus, each of the types of evoked potentials has different informativeness in diagnosing brain death. The most sensitive and specific method of acoustic stem evoked potentials. The next place is the SSVP, and the rating of the VIZ is closed. A number of authors suggest to use a complex consisting of acoustic stem, somatosensory and ZVP to improve the informativeness, use the term "multimodal evoked potentials" to designate this complex. Despite the fact that so far no large-scale multicenter studies have been conducted that determine the informativeness of multimodal evoked potentials, such studies are included as confirmatory tests in the legislation of many European countries.

In addition, it is worth noting attempts to use to confirm the death of the brain examination of the state of the blinking reflex by means of electrostimulation. The blinking reflex is identical to the corneal reflex, traditionally used in the diagnosis of the level and depth of the brain stem lesion. Its arc is closed through the bottom of the IV ventricle, respectively, with the death of the neurons of the trunk, the blinking reflex disappears along with other stem reflexes. Apparatus that provides an electrical impulse for obtaining a blinking reflex is included in the standard composition of the device for recording multimodal evoked potentials, therefore the isolated registration of the blinking reflex was not widely spread.

In addition, galvanic vestibular stimulation is of particular interest. It consists in bilateral stimulation of the region of the mastoid process with a direct current of 1 to 3 mA and a duration of up to 30 s. The direct current irritates the peripheral part of the vestibular analyzer, causing nystagmus, similar in its developmental mechanism to the caloric. Thus, the method of galvanic vestibular stimulation may be an alternative to carrying out a caloric test for traumas of the external auditory canal.

Indirect methods for diagnosing brain death

The main stage of thatogenesis of brain death is the cessation of cerebral blood flow. Consequently, the data of the instrumental study, confirming its absence for more than 30 minutes, can be absolutely accurate evidence of brain death.

One of the first methods proposed for detecting stopping intracranial blood flow was cerebral angiography. According to the recommendations, the contrast should be introduced into each test vessel under doubled pressure. The symptom of cessation of circulation is the absence of contrast in the cranial cavity, or the "stop phenomenon" observed in the internal carotid artery above the bifurcation of the common carotid artery, less often at the entrance to the temporal bone pyramid or in the siphon area and in the V ₂ or V ₃ segments of vertebrates arteries. This phenomenon should be observed in all four vessels feeding the brain: internal carotid and vertebral arteries. Special multicenter standardized studies in which the sensitivity and specificity of cerebral panangiography were accurately determined have not been carried out to date. Despite this, cerebral panagiography is included as one of the confirmatory tests in most clinical recommendations mainly as an alternative to a long follow-up period. In our opinion, the aggressive and bloody method of cerebral panangiography, which is not indifferent even to the "planned" patient, is unacceptable in the situation with the hardest patient with coma III for the following reasons.

• It is difficult to get the consent of the neuroradiologist for the implementation of cerebral panangiography to such a severe patient.
• It is incredibly difficult to move a patient in critical condition to an angiographic room. To do this, participation of at least 3 employees is required: the resuscitator who provides manual manual ventilation; a paramedic supervising a dropper with medications; an orderly who moves the patient's bed.
• One of the most crucial moments is shifting the patient to the angiographic table: in 3 of 9 observations, a cardiac arrest occurred that caused the need for defibrillation.
• The dangers of irradiation are experienced not only by patients, but also by intensive care specialists who are forced to continuously perform artificial ventilation by hand.
• The need to introduce contrast under excessively high pressure due to severe edema-tamponade of the brain in patients with cerebral coma of III-IV degree increases spasmogenicity, which can lead to the development of the so-called false carotid pseudocclusion.
• A significant disadvantage of cerebral panangiography in comparison with ultrasound methods, telethermography and EEG is that this is a one-stage study in which an angiologist receives information about the circulation of blood inside the skull within a few seconds. At the same time, it is known how different and variable the cerebral blood flow of a dying patient. Therefore, ultrasound monitoring, rather than a short-term view of the passage or stopping of contrast, is the most informative method for diagnosing brain death.
• Economic costs are significantly higher for cerebral panangiography.
• Carrying out a dying patient aggressive cerebral panagiography contradicts the basic principle of healing "Noli nosere!"
• Cases of false-negative results in trepanized patients are described.

Thus, cerebral panangiography, despite the high accuracy, can not be considered an ideal method to confirm the death of the brain.

Radionuclide diagnostic methods, in particular scintigraphy with ^99m Tc or single-photon emission CT with the same isotope, are used in many countries as a test confirming the diagnosis of "brain death". The non-occurrence of an isotope with a blood flow to the cranial cavity, called the "empty skull" phenomenon, almost completely correlates with the "stop phenomenon" observed in cerebral panangiography. Separately, it is worth noting an important symptom of brain death - a symptom of the "hot nose" , which arises from the discharge of blood from the internal carotid artery system into the outer branches that feed the facial part of the skull. This pathognomonic for brain death feature, first described in 1970, was subsequently repeatedly confirmed in numerous reports. For scintigraphy, a mobile gamma camera is usually used, which allows this study to be performed at the patient's bedside.

Thus, scintigraphy with ^99m Tc and its modifications are highly accurate, quick and feasible and relatively safe rapid diagnostic methods. However, they have one significant drawback - the inability to really assess the blood flow in the vertebrobasilar system, which is very important in the presence of only supratentorial damage. In Europe and the US, scintigraphy is included in clinical guidelines along with methods that confirm the stopping of intracranial blood flow, such as cerebral panangiography and TCD (see Chapter 11, "Ultrasonic Doppler and Duplex Scanning").

[1], [2], [3], [4], [5],